Project Summary/Abstract: Down syndrome (DS), the most common genetic cause of intellectual disability, is associated with numerous medical comorbidities, including high rates of sleep disturbance. As highlighted in the NIH Research Plan on Down Syndrome and the INCLUDE Project Research Plan, there is an urgent need to augment the field's understanding of these commonly occurring health conditions to improve quality of life for individuals with DS and those affected in the general population. An important research objective that must be met to ensure the success of clinical trials research is the validation of reliable, patient-friendly outcome measures and biomarkers to evaluate the efficacy of different treatment approaches. Both DS and sleep disturbances are associated with atypical frontal lobe structure and function as well as impaired performance on prefrontally-mediated executive function tasks. Currently, the field is lacking in valid outcome measures of prefrontal functioning for pediatric samples with DS. Thus, the proposed research aims to facilitate clinical trials research for both DS and sleep by evaluating the clinical utility of using functional near infrared spectroscopy (fNIRS) in conjunction with a developmentally appropriate executive function test battery as an outcome measure of the prefrontal hemodynamic response. The proposed study seeks to evaluate whether this tool is sensitive to the effects of both DS and sleep disturbance and can be measured in young children with DS. If funded, the proposed research will (1) test the feasibility of using fNIRS with a young sample of children with DS (ages 6-11 years, n=30) and typically developing controls matched on chronological age (TDCA [n=20; 6-11 years]) or mental age (TDMA [n=20; 3-5 years]) by quantifying the number of participants who successfully complete fNIRS data collection and examining characteristics (e.g., behavior problems, younger age) associated with task completion success; (2) evaluate whether fNIRS can detect differences in the prefrontal hemodynamic response in DS relative to chronological and mental age expectations and asses its sensitivity to the effects of sleep on the prefrontal hemodynamic response; (3) assess the clinical utility of the fNIRS-based prefrontal hemodynamic response in DS by examining relations between task-based prefrontal neural efficiency and real-world functioning (i.e., adaptive and maladaptive behavior) in this group. The proposed research represents a critical next step in clinical trials research for both DS and sleep problems. Without valid measures of key outcomes of interest for these disorders, such as prefrontal functioning, the field will be unable to fully evaluate the efficacy of different treatments that aim to improve quality life in these groups.